by Dr. C.H. Weaver M.D. updated 6/2019
Preliminary results from clinical trials in patients with early-stage non–small-cell lung cancer (NSCLC) treated with neo-adjuvant therapy were presented at the 2019 ASCO Annual Meeting and suggest that neo-adjuvant treatment is well-tolerated, and yields encouraging responses.
Currently the standard of care for the treatment of stage I-III NSCLC is surgical removal of the cancer followed by adjuvant chemotherapy administered after surgery in order to eliminate remaining cancer cells to reduce the risk of cancer recurrence. Because patients with early stage NSCLC may already have small amounts of cancer that have spread outside the lung that cannot be detected with any of the currently available tests adjuvant therapy is typically offered following surgical removal of the cancer because it reduces the risk of cancer recurrence, and improves survival. A Canadian clinical study has demonstrated that adjuvant chemotherapy increased the number of patients who lived 5 years or more from 54% to 69% and US researchers have demonstrated that adjuvant chemotherapy increased the number of patients who survived 3 years or more from 69% to 82%. Many patients however still experience a recurrence of their cancer.
Neoadjuvant therapy is treatment that is delivered before surgery with the goal of providing immediate treatment and reducing the size of the cancer for easier resection.
A large multicenter trial evaluated the benefit of neoadjuvant treatment with Tecentriq® (atezolizumab) in patients with stages IB to IIIB resectable NSCLC. Patients were treated with 2 cycles of before undergoing resection. Pretreatment with checkpoint inhibitor immunotherapy that targets PD-L1 is attractive because PD-L1 is thought to be critical for the cancer to spread.
Outcomes of the first 101 of 180 planned patients were reported. Overall, 90 patients underwent surgery and the neodjuvant immunotherapy was well tolerated. Several patients had evidence of complete or near complete disappearance of their cancer at surgery and additional information was obtained that could help further guide treatment with precision cancer medicines – the trial is ongoing.
A second trial evaluated Opdivo (nivolumab) with or without Yervoy (ipilimumab) in 44 NSCLC patients with stage I to IIIA disease. Overall 33% achieved a major pathologic response to treatment assessed at surgery. Rash and fatigue were the most common side effects.
Taken together the studies suggest that the use of neoadjuvant immunotherapy can be safely administered prior to surgery for early stage NSCLC and that significant eradication of cancer is possible. Longer follow up and comparative studies will be necessary to determine the optimal benefit of this approach – early stage NSCLC patients may want to inquire about these ongoing clinical trials.
- Kwiatkowski DJ, Rusch VW, Chaft JE, et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3). Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8503.